Ectopic expression of p27(Kip1) in oligodendrocyte progenitor cells results in cell-cycle growth arrest

Ravi Tikoo, Donna J. Osterhout, Patrizia Casaccia-Bonnefil, Prem Seth, Andrew Koff, Moses V. Chao

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Oligodendrocyte differentiation is a complex process believed to be controlled by an intrinsic mechanism associated with cell-cycle arrest. Recently, the cell-cycle inhibitor protein p27(Kip1) has been proposed as a key element in causing growth arrest of oligodendrocyte precursor cells. To investigate the effects of p27 upon oligodendrocyte cell development, we have introduced the p27 cDNA in oligodendrocyte progenitor cells using an adenovirus vector. Progenitor cells normally express low levels of p27. After adenoviral infection and p27 overexpression, progenitor cells were able to undergo cell-cycle arrest, even in the presence of strong mitogens. The effects of p27 were shown to be directly upon cyclin-dependent kinase-2 (CDK2), the protein kinase complex responsible for G1/S transition, as immunodepletion of oligodendrocyte extracts of p27 protein resulted in the activation of CDK2 activity. However, cells that became growth arrested owing to infection with p27 adenovirus did not display conventional oligodendrocyte differentiation markers, such as 04 or 01. Taken together, these data provide mechanistic evidence indicating that p27 is primarily involved in oligodendroglial progenitor proliferation by inhibiting CDK2 activity and inducing oligodendrocyte cell-cycle arrest.

Original languageEnglish
Pages (from-to)431-440
Number of pages10
JournalJournal of Neurobiology
Volume36
Issue number3
DOIs
StatePublished - 5 Sep 1998
Externally publishedYes

Keywords

  • Cell cycle
  • Cyclin-dependent kinase
  • Differentiation
  • Oligodendrocyte

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